| Autor: |
Ochayon, David E., DeVore, Stanley B., Chang, Wan-Chi, Krishnamurthy, Durga, Seelamneni, Harsha, Grashel, Brittany, Spagna, Daniel, Andorf, Sandra, Martin, Lisa J., Biagini, Jocelyn M., Waggoner, Stephen N., Khurana Hershey, Gurjit K. |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 92, p1-12, 12p |
| Abstrakt: |
Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor–α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD. Editor's summary: Atopic dermatitis (AD) manifests as skin inflammation and is often observed in children that later develop allergies and asthma. To better understand underlying immune mechanisms that contribute to AD, Ochayon et al. characterized the role for natural killer (NK) cells in children. They analyzed NK cells longitudinally in an early life cohort of children with AD and observed that children with more severe AD and allergen sensitivity had a notable accumulation of NK cells with low expression of the activating receptor NKG2D. Further analysis of a subset of children revealed that accumulation of NK cells with decreased NKG2D expression corresponded with allergen sensitization and diminished skin barrier function, and these NK cells showed decreased cytolytic activity but increased TNF-α production. Together, these observations provide critical insights into immune defects driving AD in young children. —Christiana Fogg [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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